Premature InfantNCT07262385
Calmer Brains in Very Preterm Infants
A study testing Calmer in people with Premature Infant, run by University of British Columbia at 1 site in Canada.
Trial summary
Very preterm infants in the neonatal intensive care unit (NICU) need lifesaving medical procedures which can be stressful and affect brain development. Calmer was invented to mimic key parts of parental holding (touch, heartbeat sounds and breathing motion) to help reduce stress if parents cannot be there to hold… Read more about this study
- Who is it for?
- Ages 26 to 30 weeks
- Conditions the study is for
- Premature Infant
- What is being tested?
- Calmer
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 1 Dec 2025to Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 26 to 30 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Very preterm infants admitted to the NICU at the BC Women's Hospital
Who cannot join
- Congenital anomalies;
- Born small for GA (per medical admission history);
- History of birthing parent substance use in pregnancy;
- Ongoing infection at the time of enrollment;
- Pre-existing cardiovascular instability defined by shock/hypotension/need for cardiovascular drugs;
- Receiving paralytic drugs;
- Major neurological injury (e.g. hypoxic ischemic encephalopathy, hemorrhage/stroke; VP shunt);
- Beyond the 30th completed week GA (30 weeks + 6 days) at enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
BC Women's Hospital & Health Centre
Vancouver, British Columbia, V6H 3N1
Manon Ranger, PhD, 604-827-1382, manon.ranger@ubc.ca
Manon Ranger, PhD
About this study
Official title: Calmer Brains: A Pilot Randomized Trial to Explore Structural and Functional Brain Development in Preterm Infants
Very preterm infants in the neonatal intensive care unit (NICU) need lifesaving medical procedures which can be stressful and affect brain development. Calmer was invented to mimic key parts of parental holding (touch, heartbeat sounds and breathing motion) to help reduce stress if parents cannot be there to hold their infant. Using specialized brain scans done at full term, we will gather initial information in 22 infants born 3-4 months early to compare brain development in infants who receive Calmer at least 3 hours each day (+ regular NICU care) over 2-3 weeks with infants who have regular NICU care.
Read the detailed description
Very preterm infants (< 32 weeks gestational age [GA]) experience developmentally unexpected, repeated stress as part of lifesaving care in the NICU during a period of considerable brain maturation and growth. Exposure to early-life stress alters brain maturation resulting in long-term changes in neurodevelopment. Parental skin-to-skin care (SSC) can mitigate stress; however, parents are not always available. Calmer, a patented, therapeutic medical device, was invented to simulate aspects of SSC (skin-like surface, breathing motion, heartbeat sounds) with rates of the latter two individualized for each infant. In a randomized trial, Calmer has been shown to stabilize brain blood flow during a single, routine blood test. Most recently, we found that very preterm infants who received Calmer treatment for 3 continuous weeks had 25% greater head growth compared to controls. However, we do not know if/how Calmer treatment affects brain development in very preterm infants.
Objectives: We will gather pilot data for a larger trial to examine differences in brain structural and functional development in very preterm infants who receive Calmer treatment for 2-3 consecutive weeks compared to controls.
Methods: 22 infants born 26-30 weeks GA admitted to BC Women's Hospital NICU will be randomized to either control (n=11) or treatment groups (n=11; Calmer for 2-3 continuous weeks, 3 hours/day minimum treatment). Infants from both groups will undergo feed and bundle MRI scans at term-equivalent age using high resolution volumetric, diffusion and resting-state functional MRI to explore group differences in whole-brain volumes and structural and functional connectivity. Images will be processed using existing quantitative neonatal imaging analysis pipelines in the Selvanathan and Weber labs at BC Children's Hospital Research Institute. Analyses will include: measures of trial feasibility and description of brain differences between groups.
Significance: Ultimately, Calmer may support healthy brain maturation optimizing the neurodevelopment of vulnerable infants in Canada and beyond.
- Conditions
- Premature Infant
- Being tested
- Calmer
- Keywords
- Prematurity, Brain development, Stress, NICU, Pilot RCT, Feasibility, Calmer - therapeutic medical device
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CalmerDevice
Calmer, a unique, patented, therapeutic bed that mimics key aspects of SSC that reduce stress in preterm infants. Calmer fits into NICU incubators and cribs, and delivers 3 key SSC stimuli: touch, breathing motion, and heartbeat sounds; the rates of the latter 2 stimuli are individualized to each infant based on their parents' breathing and heart rates. Calmer is designed to provide complementary care only when parents are not able to give SSC. It is not meant nor designed to replace human SSC, so will never be tested as such a replacement. Instead, Calmer was invented to enhance and optimize brain development in preterm infants by reducing stress during the NICU stay, when parents/caregivers are not available for SSC. Our ultimate goal is to enable use of Calmer from an infant's admission to discharge, only during those times when caregivers are not available.
| Study group | Role | What they receive |
|---|---|---|
| Calmer | Experimental | Infants in the Calmer group will have a Calmer* placed and left in their incubators for a minimum of 2 and maximum of 3 weeks and will receive treatment for a minimum cumulative total of 3 hours/day (i.e. time can be discontinuous).
Each day, after the infant's parent rests for 10 minutes, the research and/or bedside nurse will record the heart and respiratory rates for a 2-minute period (or taken by the caregiver themselves after training by research/NICU staff). The 1-minute average will be used to program Calmer for each infant that day to better simulate day-to-day changes in infant-parent contact. The values can be adjusted over the day as parents wish.
*Calmer, a patented, therapeutic bed that mimics key aspects of skin-to-skin care (SSC) to reduce stress in preterm infants. Calmer fits into NICU incubators and delivers 3 key SSC stimuli: touch, breathing motion, and heartbeat sounds (rates individualized to each infant based on their parents' HR/RR). Receives: Device: Calmer |
| Control | No intervention | Infants in the Control group will receive standard NICU care, including parent SSC. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain Volumes
Anatomical analysis: Anatomical images (T2w) will be manually inspected for quality control. Images with very poor tissue contrast or motion artefacts will be rejected. T2w images will be bias-field corrected using ANTs N4ITK. The images will then be skull-stripped and segmented using the dHCP anatomical pipeline to calculate total and sub-regional brain volumes.
Measured: When each participant reaches 40 weeks post-conceptual age and return for their MRI scan
Brain Functional Connectivity
Resting state fMRI analysis: Fieldmaps will be generated using the dual-echo EPI and magnitude scan. The dHCP functional pipeline will be implemented to achieve distortion-correction and motion-correction, register the functional image to the corresponding T2w structural image, generate a transform matrix from functional space to the 40-week T2w template; and we will perform temporal high-pass filtering (150 s high-pass cutoff) and independent component analysis (ICA) denoising using ICA FIX. Scans with a mean FD > 1 mm will be excluded. The dHCP functional pipeline will then be run on all subjects using the study-specific training file. Spatial smoothing of 5 mm will be applied using FSL's SUSAN and grand mean intensity normalization will be computed. Functional connectivity measures will be computed using the CONN toolbox.
Measured: When each participant reaches 40 weeks post-conceptual age
Brain Fractional Anisotropy
Diffusion tensor imaging analysis: The dHCP neonatal dMRI data processing pipeline will be used to pre-process the diffusion weighted images. Briefly, opposite phase b0 images are used to estimate the off-resonance field that is then used in the simultaneous correction of motion artefacts, susceptibility-induced and eddy current distortions. Data will then be super-resolved and, after pre-processing is complete, local diffusion and microstructural models are fitted in every voxel and averaged to calculate mean fractional anisotropy.
Measured: When participants reach term-equivalent age
Secondary outcomes (2)
Clinical weight measures
Weight: infant weight in kilograms captured when enrolled in the study (i.e. baseline T1) and end of experimental phase (2-3 weeks later; T2)
We will use the weight measure to determine changes between baseline and the end of treatment.
Measured: From the start of study treatment (or enrolment if Control group) to 2-3 weeks later, at the end of intervention exposure.
Head growth measures
Head circumference: infant head circumference in centimetres (occipito-frontal circumference) captured when enrolled in the study (i.e. baseline T1) and end of experimental phase (2-3 weeks later; T2).
We will use the head circumference measures to determine changes between baseline and the end of treatment.
Measured: From the start of study treatment (or enrolment if Control group) to 2-3 weeks later, at the end of intervention exposure.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2025
- Study start1 Dec 2025 (estimated)
- Primary completionApr 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Premature InfantStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- We will conduct a single-site, single-blind, two-group (treatment and control), randomized pilot trial and determine the feasibility of our study design. We will also gather preliminary data of Calmer's effect on infant structural and functional brain development to inform a larger trial.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- BC Children's Hospital Research Institute
- Responsible party
- Principal investigator, Manon Ranger, University of British Columbia
- Investigators
- Manon Ranger, PhD, Principal investigator, University of British ColumbiaLiisa Holsti, PhD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07262385
- Sponsor's protocol ID
- H25-01015
- Status last verified
- Nov 2025
- First submitted
- 4 Jul 2025
- Last updated
- 3 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: As part of this study, participants' de-identified research data may be shared in a public database when the research is published. Sharing this deidentified data helps make research more transparent and allows others to double-check the results. It also means that other researchers can use the data for different studies in the future, beyond the scope of this current study. The exact details have not been decided yet.
Publications
Holsti L, MacLean K, Oberlander T, Synnes A, Brant R. Calmer: a robot for managing acute pain effectively in preterm infants in the neonatal intensive care unit. Pain Rep. 2019 Mar 14;4(2):e727. doi: 10.1097/PR9.0000000000000727. eCollection 2019 Mar-Apr.
PubMed 31041426Ranger M, Albert A, MacLean K, Holsti L. Cerebral hemodynamic response to a therapeutic bed for procedural pain management in preterm infants in the NICU: a randomized controlled trial. Pain Rep. 2021 Jan 12;6(1):e890. doi: 10.1097/PR9.0000000000000890. eCollection 2021 Jan-Feb.
PubMed 33490850
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Calmer Brains: A Pilot Randomized Trial to Explore Structural and Functional Brain Development in Preterm Infants
- ClinicalTrials.gov ID
- NCT07262385
- Acronym / sponsor ID
- H25-01015
- Conditions
- Premature Infant
- Keywords
- Prematurity, Brain development, Stress, NICU, Pilot RCT, Feasibility, Calmer - therapeutic medical device
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- BC Children's Hospital Research Institute
- Study start
- 1 Dec 2025 (estimated)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 3 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Very preterm infants in the neonatal intensive care unit (NICU) need lifesaving medical procedures which can be stressful and affect brain development. Calmer was invented to mimic key parts of parental holding (touch, heartbeat sounds and breathing motion) to help reduce stress if parents cannot be there to hold their infant. Using specialized brain scans done at full term, we will gather initial information in 22 infants born 3-4 months early to compare brain development in infants who receive Calmer at least 3 hours each day (+ regular NICU care) over 2-3 weeks with infants who have regular NICU care.
Detailed description
Very preterm infants (< 32 weeks gestational age [GA]) experience developmentally unexpected, repeated stress as part of lifesaving care in the NICU during a period of considerable brain maturation and growth. Exposure to early-life stress alters brain maturation resulting in long-term changes in neurodevelopment. Parental skin-to-skin care (SSC) can mitigate stress; however, parents are not always available. Calmer, a patented, therapeutic medical device, was invented to simulate aspects of SSC (skin-like surface, breathing motion, heartbeat sounds) with rates of the latter two individualized for each infant. In a randomized trial, Calmer has been shown to stabilize brain blood flow during a single, routine blood test. Most recently, we found that very preterm infants who received Calmer treatment for 3 continuous weeks had 25% greater head growth compared to controls. However, we do not know if/how Calmer treatment affects brain development in very preterm infants.
Objectives: We will gather pilot data for a larger trial to examine differences in brain structural and functional development in very preterm infants who receive Calmer treatment for 2-3 consecutive weeks compared to controls.
Methods: 22 infants born 26-30 weeks GA admitted to BC Women's Hospital NICU will be randomized to either control (n=11) or treatment groups (n=11; Calmer for 2-3 continuous weeks, 3 hours/day minimum treatment). Infants from both groups will undergo feed and bundle MRI scans at term-equivalent age using high resolution volumetric, diffusion and resting-state functional MRI to explore group differences in whole-brain volumes and structural and functional connectivity. Images will be processed using existing quantitative neonatal imaging analysis pipelines in the Selvanathan and Weber labs at BC Children's Hospital Research Institute. Analyses will include: measures of trial feasibility and description of brain differences between groups.
Significance: Ultimately, Calmer may support healthy brain maturation optimizing the neurodevelopment of vulnerable infants in Canada and beyond.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- We will conduct a single-site, single-blind, two-group (treatment and control), randomized pilot trial and determine the feasibility of our study design. We will also gather preliminary data of Calmer's effect on infant structural and functional brain development to inform a larger trial.
| Arm | Type | Receives |
|---|---|---|
| Calmer | Experimental | Device: CalmerInfants in the Calmer group will have a Calmer* placed and left in their incubators for a minimum of 2 and maximum of 3 weeks and will receive treatment for a minimum cumulative total of 3 hours/day (i.e. time can be discontinuous). Each day, after the infant's parent rests for 10 minutes, the research and/or bedside nurse will record the heart and respiratory rates for a 2-minute period (or taken by the caregiver themselves after training by research/NICU staff). The 1-minute average will be used to program Calmer for each infant that day to better simulate day-to-day changes in infant-parent contact. The values can be adjusted over the day as parents wish. *Calmer, a patented, therapeutic bed that mimics key aspects of skin-to-skin care (SSC) to reduce stress in preterm infants. Calmer fits into NICU incubators and delivers 3 key SSC stimuli: touch, breathing motion, and heartbeat sounds (rates individualized to each infant based on their parents' HR/RR). |
| Control | No intervention | –Infants in the Control group will receive standard NICU care, including parent SSC. |
Who may qualify
- Ages
- 26 to 30 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Very preterm infants admitted to the NICU at the BC Women's Hospital
Key exclusion criteria (8 listed)
- Congenital anomalies;
- Born small for GA (per medical admission history);
- History of birthing parent substance use in pregnancy;
- Ongoing infection at the time of enrollment;
- Pre-existing cardiovascular instability defined by shock/hypotension/need for cardiovascular drugs;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CalmerCalmer, a unique, patented, therapeutic bed that mimics key aspects of SSC that reduce stress in preterm infants. Calmer fits into NICU incubators and cribs, and delivers 3 key SSC stimuli: touch, breathing motion, and heartbeat sounds; the rates of the latter 2 stimuli are individualized to each infant based on their parents' breathing and heart rates. Calmer is designed to provide complementary care only when parents are not able to give SSC. It is not meant nor designed to replace human SSC, so will never be tested as such a replacement. Instead, Calmer was invented to enhance and optimize brain development in preterm infants by reducing stress during the NICU stay, when parents/caregivers are not available for SSC. Our ultimate goal is to enable use of Calmer from an infant's admission to discharge, only during those times when caregivers are not available. | Device | Calmer |
Primary outcome
Brain Volumes
Time frame: When each participant reaches 40 weeks post-conceptual age and return for their MRI scan
Anatomical analysis: Anatomical images (T2w) will be manually inspected for quality control. Images with very poor tissue contrast or motion artefacts will be rejected. T2w images will be bias-field corrected using ANTs N4ITK. The images will then be skull-stripped and segmented using the dHCP anatomical pipeline to calculate total and sub-regional brain volumes.
Brain Functional Connectivity
Time frame: When each participant reaches 40 weeks post-conceptual age
Resting state fMRI analysis: Fieldmaps will be generated using the dual-echo EPI and magnitude scan. The dHCP functional pipeline will be implemented to achieve distortion-correction and motion-correction, register the functional image to the corresponding T2w structural image, generate a transform matrix from functional space to the 40-week T2w template; and we will perform temporal high-pass filtering (150 s high-pass cutoff) and independent component analysis (ICA) denoising using ICA FIX. Scans with a mean FD > 1 mm will be excluded. The dHCP functional pipeline will then be run on all subjects using the study-specific training file. Spatial smoothing of 5 mm will be applied using FSL's SUSAN and grand mean intensity normalization will be computed. Functional connectivity measures will be computed using the CONN toolbox.
Brain Fractional Anisotropy
Time frame: When participants reach term-equivalent age
Diffusion tensor imaging analysis: The dHCP neonatal dMRI data processing pipeline will be used to pre-process the diffusion weighted images. Briefly, opposite phase b0 images are used to estimate the off-resonance field that is then used in the simultaneous correction of motion artefacts, susceptibility-induced and eddy current distortions. Data will then be super-resolved and, after pre-processing is complete, local diffusion and microstructural models are fitted in every voxel and averaged to calculate mean fractional anisotropy.
2 secondary outcomes
Clinical weight measures
Time frame: From the start of study treatment (or enrolment if Control group) to 2-3 weeks later, at the end of intervention exposure.
Head growth measures
Time frame: From the start of study treatment (or enrolment if Control group) to 2-3 weeks later, at the end of intervention exposure.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2025.
- Results publication: PubMed 31041426Holsti L, MacLean K, Oberlander T, Synnes A, Brant R. Calmer: a robot for managing acute pain effectively in preterm infants in the neonatal intensive care unit. Pain Rep. 2019 Mar 14;4(2):e727. doi: 10.1097/PR9.0000000000000727. eCollection 2019 Mar-Apr.
- Results publication: PubMed 33490850Ranger M, Albert A, MacLean K, Holsti L. Cerebral hemodynamic response to a therapeutic bed for procedural pain management in preterm infants in the NICU: a randomized controlled trial. Pain Rep. 2021 Jan 12;6(1):e890. doi: 10.1097/PR9.0000000000000890. eCollection 2021 Jan-Feb.
- Individual participant dataSharing planned: Yes. As part of this study, participants' de-identified research data may be shared in a public database when the research is published. Sharing this deidentified data helps make research more transparent and allows others to double-check the results. It also means that other researchers can use the data for different studies in the future, beyond the scope of this current study. The exact details have not been decided yet.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Manon Ranger, PhD principal investigator
University of British Columbia
Liisa Holsti, PhD principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Calmer in people with Premature Infant, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Manon Ranger, PhD (604-827-1382, manon.ranger@ubc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain Volumes (time frame: When each participant reaches 40 weeks post-conceptual age and return for their MRI scan). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07262385, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2025.